Human T cell responses to Japanese encephalitis virus in health and disease.

J Exp Med

Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, England, UK Health Protection Research Unit for Emerging and Zoonotic Infections, University of Liverpool, Liverpool L69 7BE, England, UK Walton Center National Health Service Foundation Trust, Liverpool L9 7LJ, England, UK.

Published: June 2016

Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8(+) and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4(+) and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4(+) T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4(+) and CD8(+) T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925015PMC
http://dx.doi.org/10.1084/jem.20151517DOI Listing

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